药学学报, 2018, 53(9): 1414-1421
许海燕, 彭修娟, 陈衍斌, 许刚, 逯莉, 侯敏娜, 刘艳红, 刘峰, 许海玉. 基于网络药理学的“柴胡−黄芩”药对治疗糖尿病的“理法−方药−成分−靶标−活性”关联研究[J]. 药学学报, 2018, 53(9): 1414-1421.
XU Hai-yan, PENG Xiu-juan, CHEN Yan-bin, XU Gang, LU Li, HOU Min-na, LIU Yan-hong, LIU Feng, XU Hai-yu. Exploration of “principle-recipe-composition-target-activity” association of Bupleuri Radix and Scutellariae Radix drug pair for diabetes treatment based on network pharmacology[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1414-1421.

许海燕1, 彭修娟1, 陈衍斌2, 许刚2, 逯莉1, 侯敏娜1, 刘艳红1, 刘峰1,2, 许海玉1,3
1. 陕西国际商贸学院, 陕西 咸阳 712046;
2. 陕西步长制药有限公司, 陕西 西安 710075;
3. 中国中医科学院中药研究所, 北京 100700
关键词:    网络药理学      柴胡-黄芩      药对      糖尿病      理法-方药-成分-靶标-活性     
Exploration of “principle-recipe-composition-target-activity” association of Bupleuri Radix and Scutellariae Radix drug pair for diabetes treatment based on network pharmacology
XU Hai-yan1, PENG Xiu-juan1, CHEN Yan-bin2, XU Gang2, LU Li1, HOU Min-na1, LIU Yan-hong1, LIU Feng1,2, XU Hai-yu1,3
1. Shaanxi Institute of International Trade and Commerce, Xianyang 712046, China;
2. Shaanxi Buchang Pharmaceutical Co., Ltd., Xi'an 710075, China;
3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
By using the integrated pharmacology platform and the big data of traditional Chinese medicine combined with the pharmacology thinking of "principle-recipe-composition-target-pathway-activity" in this study, we predicted the material basis and mechanisms of Bupleuri Radix and Scutellariae Radix drug pair for the treatment of diabetes. Fifty-nine active components were predicted, which included saponins, flavones, essential oil, fatty acids and so on. They acted on twenty-two direct targets and twenty-six main pathways respectively.The known disease targets of diabetes include arginine vasopressin receptor gene (AVP), retinoblastoma (RB1), receptor active modified protein (RAMP), platelet growth factor receptor (PDGFR), insulin receptor (INSR), α-glucosidase (GAA), etc. The pathways with diabetes effect involves endocrine system, circulatory system, digestive system, thyroid hormone signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway, lipid metabolism and other related biological processes and metabolic pathways. The results of virtual screening in molecular docking technology indicate that flavonoids from Bupleuri Radix and Scutellariae Radix drug pair can easily form good docking mode and high affinity with peroxisome proliferators activated receptor γ (PPAR-γ) and glycogen synthase kinase-3β (GSK-3β), showing antidiabetic activity. The study provides information for the treatment of diabetes by Bupleuri Radix and Scutellariae Radix drug pair, and a new thought for the study of drug pair and complex prescription.
Key words:    network pharmacology    Bupleuri Radix and Scutellariae Radix    drug pair    diabetes    principlerecipe-composition-target-activity   
收稿日期: 2018-04-17
DOI: 10.16438/j.0513-4870.2018-0354
基金项目: 十三五重大新药创制(2018ZX09721005-004-007);陕西省科技厅项目(2016SF-378).
通讯作者: 刘峰,Tel:86-29-33694603,E-mail:liufeng1720@163.com;许海玉,Tel:86-10-64014411,E-mail:hy_xu627@163.com
Email: liufeng1720@163.com;hy_xu627@163.com
PDF(424KB) Free
许海燕  在本刊中的所有文章
彭修娟  在本刊中的所有文章
陈衍斌  在本刊中的所有文章
许刚  在本刊中的所有文章
逯莉  在本刊中的所有文章
侯敏娜  在本刊中的所有文章
刘艳红  在本刊中的所有文章
刘峰  在本刊中的所有文章
许海玉  在本刊中的所有文章

[1] Chen XF. Drug Screening and Mechanism of Chinese Medicine for Diabetes Mellitus based on Literature Mining (基于文献挖掘的中药治疗糖尿病用药筛选及作用机制研究)[D]. Beijing:Beijing University of Chinese Medicine, 2016.
[2] Shi JB, Huang BY, Liu F. Clinical observation on Dachaihu Decotion in treating pre-diabetes with syndrome of heat stagnation in liver and stomach[J]. Chin Med Mod Dis Edu China (中国中医药现代远程教育), 2017, 15:72-74.
[3] Tao J, Jiang M, Chen LY, et al. Mechanism study of prescription to treat Xiaoke based on the property and flavor theory of Chinese medicine and network pharmacology[J]. Acta Pharm Sin (药学学报), 2017, 52:236-244.
[4] Zhang YQ, Guo QY, Li QY, et al. Main active constituent identification in Guanxinjing capsule, a traditional Chinese medicine, for the treatment of coronary heart disease complicated with depression[J]. Acta Pharmacol Sin, 2018, 39:975-987.
[5] Zhang YQ, Mao X, Su J, et al. A network pharmacologybased strategy deciphers the underlying molecular mechanisms of Qixuehe Capsule in the treatment of menstrual disorders[J]. Chin Med, 2017, 12:23-31.
[6] Yu G, Zhang Y, Ren W, et al. Network pharmacology-based identification of key pharmacological pathways of Yin-HuangQing-Fei capsule acting on chronic bronchitis[J]. Int J Chron Obstruct Pulmon Dis, 2017, 12:85-94.
[7] Peng XJ, Yang XJ, Chen YB, et al. Action mechanism of Baihe Dihuang decoction on depression based on integrative pharmacology of traditional Chinese medicine[J]. Chin J Chin Mater Med (中国中药杂志), 2018, 43:1338-1344.
[8] Pan H. Efficacy of Chaihuqinggantang and Western Medicine Treated Patients with Bacterial Liver Abscess with Type 2 Diabetes Mellitus (柴胡清肝汤联合西医治疗合并糖尿病的细菌性肝脓肿疗效观察)[D]. Tianjin:Tianjin Medical University, 2017.
[9] Li PT. Study in Chemical Component Changes and RCT Effects of Radix Bupleuri and Its TCM Compatibility (柴胡药对配伍对皂苷类成分影响及调节RCT的实验研究)[D]. Guangzhou:Guangzhou University of Traditional Chinese Medicine, 2016.
[10] Pan XP, Xing ZL, Jia WG, et al. Identification and preparation of a glycol-protein fraction AN from tea extracts and its in vivo and in vitro anti-hyperglycosemia activity[J]. Chin J Chin Mater Med (中国中药杂志), 2018, 43:736-742.
[11] Huang Q. Study on Long-chain Fatty Acid Receptors:Agonists Screening and Pharmacological Investigations of the Anti-diabetic Effect (长链脂肪酸受体激动剂筛选及其抗糖尿病药理机制研究)[D]. Shanghai:University of Chinese Academy of Sciences, 2017.
[12] Ogawa S, Abe T, Nako K, et al. Eicosapentaenoic acid improve glycemic control in elderly bedridden patients with type 2 diabetes[J]. Tohoku J Exp Med, 2013, 231:63-74.
[13] Yanai H, Hamasaki H, Katsuyama H, et al. Effects of intake of fish or fishoils on the development of diabetes[J]. J Clin Med Res, 2015, 7:8-12.
[14] Pang GC, Chen QS, Hu ZH, et al. On the relationship between food nutrition and immunometabolism[J]. Food Sci (食品科学), 2018, 39:1-15.
[15] Huang YB, Zhang LX, Zhang LQ. Clinical characteristic analysis of type 2 diabetes mellitus complicated with digestive system malignant tumor[J]. Clin J Med Offic (临床军医杂志), 2015, 43:43-47.
[16] Li SW, Xia W, Deng HH, et al. Effect of haplotype in fatty acid desaturase gene on plasma lipids and fatty acids in type 2 diabetes mellitus[J]. Chin J Diabetes (中国糖尿病杂志), 2018, 26:3-9.
[17] Du M. Relation between Hypernatremia and Urine Sodium in Critical Patients (重症患者高钠血症与尿钠关系研究)[D]. Guangzhou:Southern Medical University, 2015.
[18] Jiang NN, Guo MF, Gao JR, et al. Mechanism of Huangdi Anxiao capsules improving insulin resistance in spontaneous T2DM rats[J]. Pharmacol Clin Chin Mater Clin Med (中药药理与临床), 2017, 33:109-114.
[19] Fu LJ, Hu MH, Ying XQ, et al. Therapeutic effects of leaf extract from Cyclocarya paliurus on rats with type 2 diabetes mellitus[J]. Chin Tradit Pat Med (中成药), 2017, 39:1134-1138.
[20] Hong JN, Yang JX, Wang XM. Research progress in hypoglycemic effect and mechanism of heat-clearing and detoxifying Chinese materia medica[J]. Chin Tradit Herbal Drugs (中草药), 2015, 46:2656-2662.
[21] Wang JH, Ou Y. Glucokinase and diabetes mellitus[J]. Pharm Biotechnol (药物生物技术), 2012, 19:552-556.
[22] Zhang BX, Kong Q, Zhao HL, et al. Association between C-106T gene polymorphisms of aldose reductase and diabetic kidney disease in Chinese with type 2 diabetes[J]. J China Japan Friendship Hosp (中日友好医院学报), 2015, 29:352-358.
[23] Wang QH. Engineered Ubiquitin Ligase PTB-U-box Targets Insulin/Insulin-like Growth Factor Receptor for Degradation and Inhibits Tumor Malignancy (PTB-U-box靶向性降解胰岛素样生长因子受体和胰岛素受体的肿瘤治疗策略)[D] Xi'an:Forth Military Medical University, 2014.
[24] Chi YJ, Li J, Guang YF, et al. PI3K/Akt signaling axis in regulation of glucose homeostasis[J]. Chin J Biochem Mol Biol (中国生物化学与分子生物学报), 2010, 26:879-885.
[25] Hao BJ, Liu X, Zhao ZC, et al. Quantitative analysis and developing trends of anti-type 2 diabetes drug targets[J]. Chin New Drug (中国新药杂志), 2013, 22:1236-1242.
[26] Liang Y, Mei J. Relationship between thyroid hormone level and metabolic syndrome in patients with type 2 diabetes mellitus[J]. J Parct Diabetol (临床糖尿病杂志), 2018, 14:43-45.
[27] Lei L, Gu C, Hu M, et al. Change of Erb B2 expression and phospho-Erb B2 level in diabetic cardiomyopathy rats[J]. South China J Cardiovasc Dis (岭南心血管病杂志), 2011, 17:228-232.
[28] Yu JJ, Hua F, Hu ZW. Advances in the studies of the link between diabetes and cancer[J]. Acta Pharm Sin (药学学报), 2016, 57:1017-1025.
[29] Ma X, Wang YY, Yang WS, et al. Meta-analysis of type 2 diabetes and the risk of reproductive system malignancy[J]. China Cancer (中国肿瘤), 2014, 23:265-275.
[30] Fu XL, Tian YL, Zang ZD, et al. Clinical study on correlation between type 2 diabetes mellitus or impaired glucose tolerance and hepatocellular carcinoma in patients with hepatitis B cirrhosis[J]. Oncol Prog (癌症进展), 2017, 15:540-544.
[31] He XX, Shang CY, Chang B, et al. Investigation on big data and visualized relationship between cancer and diabetes[J]. J Xinjiang Med Univ (新疆医科大学学报), 2017, 40:229-232.
[32] Liu MH. Pharmaceutical and Pharmacokinetic Research on Radix Scutellare and Radix Bupleuri in Compatibility (药对配伍对柴胡-黄芩主要药效作用影响的研究)[D]. Shandong:Shandong Traditional Chinese Medicine University, 2011.
[33] Yang JP. The Research of The Effective Fraction about Antifebrile Action from Bupleurum Chinese-Scutellaria and Its Compatibility Mechanism (柴胡-黄芩药对退热有效部位及其配伍作用机制的研究)[D]. Beijing:Beijing University of Chinese Medicine, 2012.
[34] Xie SY. Study on Quality of Life of Xiao Chaihu Decoction on Type 2 Diabetes Mellitus with Shaoyang Syndrome (小柴胡汤加减治疗少阳型消渴病(2型糖尿病)的生存质量研究)[D]. Guangzhou:Guangzhou University of Chinese Medicine, 2017.
[35] Cui X, Shang EX, Jiang S, et al. Interaction of ScutellariaCoptis herb pair in improvement of glucose and lipid metabolism of type 2 diabetes rats based on response surface method[J]. Acta Pharm Sin (药学学报), 2018, 53:630-635.
[36] Xiao Y, Xiao B, Zhao N, et al. Screening of PPAR-γ agonist active ingredient of flavonoids from Artemisia ordosica by molecular docking technology[J]. J China Pharm (中国药房), 2018, 29:58-62.
[37] Song J, Gao XX, Tian JS, et al. Modern research on compatibility mechanism of Chinese materia medica pair[J]. Chin Tradit Herbal Drugs (中草药), 2017, 48:4367-4374.
[38] Tang YP, Duan JA. Drug Pair Modern Research (药对现代研究)[M]. Beijing:Science Press, 2014:3-7.
[39] Xu HY, Huang LQ, Lu P, et al. Application of ADME process in vivo in combination with network pharmacology in study of traditional Chinese medicine[J]. Chin J Chin Mater Med (中国中药杂志), 2012, 37:142-146.
[40] Pang B. Heritage Research on The Academic Thoughts and Experience of Prestigious TCM Doctors from Shi Jinmo's School in The Diagnosis and Treatment of Diabetes (施今墨学派名老中医诊治糖尿病学术思想与经验传承研究)[D]. Beijing:Beijing University of Chinese Medicine, 2012.
1.宋勇丽, 王政霖, 邢玮, 吴晏, 王伟, 韩静.基于网络药理学的复方血栓通治疗糖尿病视网膜病的药理机制研究[J]. 药学学报, 2018,53(9): 1442-1448